The ultimate goal of this project is to develop artificial lung assist device technology to treat acute and chronic pulmonary failure. Chronic lung disease is the third-leading cause of death in the United States, exceeded only by heart disease and cancer. Currently there are no long-term solutions for chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD) other than lung transplantation, and a severe shortage of donor organs limits this approach, leaving most patients relying on home oxygen therapy. For acute illnesses such as Adult Respiratory Distress Syndrome (ARDS), mechanical ventilation is typically required, and complications and mortality remain very high. Alternatives such as ExtraCorporeal Membrane Oxygenator (ECMO) therapy can only be used for a limited duration require high levels of anticoagulation and involve numerous operational complexities. There is an urgent need for technological advances in artificial lung devices, including simplification and extended use of devices, a reduced need for anticoagulation, and high gas transfer rates in a compact format with low blood volumes. Here we propose an Exploratory Bioengineering Research Grant to pursue the development of technology for a bioartificial lung, based on biomimetic design principles and microfabrication technology to build scalable respiratory assist architectures capable of high levels of gas transport in a small and compact structure. Successful development of a bioartificial lung will require several critical elements, many of which have not been realized because of difficulties in mimicking natural lung physiology due to limitations in fabrication technology. The specific aims of this proposal are directed towards these elements, including the ability to design a biomimetic structure with small priming volume and high levels of gas permeability, and the establishment of an endothelialized microvascular network to support smooth blood flow without clotting in the absence of anticoagulative agents. These goals are consistent with future clinical targets including the ability to provide patients with long-term functional respiratory assist devices that do not require extensive anticoagulation and that can be enabled in a wearable or potentially implantable format. To accomplish these goals, we aim 1) To generate a biomimetic design and utilize microfabrication technology to construct an artificial lung module comprising microvascular networks and gas-permeable membranes, and 2) To establish endothelialized microfluidic network in vascular chamber and determine gas transport and blood flow coagulation properties of bioartificial lung construct. PUBLIC HEALTH RELEVANCE: The ultimate goal of this project is to develop a medical device capable of oxygenating the blood of patients suffering from acute and chronic lung diseases and cardiopulmonary failure. Current technologies cannot be used for more than one month, require high levels of anti-clotting agents, and often damage sensitive lung tissues. This new technology will mimic the structure and function of natural, healthy lungs and provide a long- term treatment for patients suffering from acute lung injury, chronic obstructive pulmonary disease, and other conditions that cause hypoxia.